基质金属蛋白酶组织抑制剂 3 抑制结构域与苏拉明、硫酸软骨素和戊聚糖多硫酸酯相互作用的热力学特性。
Thermodynamic profiles of the interactions of suramin, chondroitin sulfate, and pentosan polysulfate with the inhibitory domain of TIMP-3.
机构信息
Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.
Integrated Medical Sciences Department, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.
出版信息
FEBS Lett. 2020 Jan;594(1):94-103. doi: 10.1002/1873-3468.13556. Epub 2019 Sep 13.
Extracellular levels of soluble TIMP-3 are low, reflecting its binding by extracellular matrix (ECM) components including sulfated glycosaminoglycans (SGAGs) and endocytosis via low density lipoprotein receptor-related protein 1. Since TIMP-3 inhibits ECM degradation, the ability of SGAGs to elevate extracellular TIMP-3 is significant for osteoarthritis treatment. Previous studies of such interactions have utilized immobilized TIMP-3 or ligands. Here, we report the thermodynamics of the interactions of the sGAG-binding N-domain of TIMP-3 with chondroitin sulfate, pentosan polysulfate, and suramin in solution using isothermal titration calorimetry. All three interactions are driven by a favorable negative enthalpy change combined with an unfavorable decrease in entropy. The heat capacity changes (ΔC ) for all of the interactions are zero, indicating an insignificant contribution from hydrophobic interactions.
细胞外 TIMP-3 的水平较低，这反映了它与细胞外基质（ECM）成分的结合，包括硫酸化糖胺聚糖（SGAG）和通过低密度脂蛋白受体相关蛋白 1 的内吞作用。由于 TIMP-3 抑制 ECM 降解，因此 SGAG 升高细胞外 TIMP-3 的能力对骨关节炎的治疗具有重要意义。以前对这种相互作用的研究利用了固定化 TIMP-3 或配体。在这里，我们使用等温滴定量热法报告了 TIMP-3 的 sGAG 结合 N 结构域与硫酸软骨素、戊聚糖多硫酸酯和苏拉明在溶液中的相互作用的热力学。所有三种相互作用都是由有利的负焓变化和不利的熵降低驱动的。所有相互作用的热容变化（ΔC）均为零，表明疏水相互作用的贡献可以忽略不计。
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